A Prospective Study of Bortezomib in Combination with Melphalan and Prednisone for Patients with Previously Untreated Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5181-5181 ◽  
Author(s):  
Cristina Gasparetto ◽  
George P. Keogh ◽  
Jon P. Gockerman ◽  
Mitchell Horwitz ◽  
Joseph O. Moore ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Prospective Study ◽  
Partial Remission ◽  
Response Rate ◽  
High Dose ◽  
The Usa ◽  
M Spike ◽  
A Prospective Study ◽  
Stem Cell Collection

Abstract The standard induction chemotherapy for patients with multiple myeloma (MM) is a dexamethasone based regimen including dexamethasone alone, VAD, thalidomide+dexamethasone and other combinations. Currently the overall response rate achieved with these regimens is ≤70% and the complete remission (CR) rate is <10%. In order to improve the CR rate for both transplant and non-transplant candidates, other agents and regimens are being explored. Bortezomib (Velcade), a proteasome inhibitor currently approved in the USA and in Europe for the treatment of relapsed/refractory MM, has demonstrated an impressive activity in the treatment of myeloma. In relapsed/refractory MM, bortezomib has achieved response rate of 35%, with a median duration of response and overall survival of 14 and 18 months, respectively. Clinical experience in relapsed/refractory MM and in previously untreated patients has suggested that the combination of bortezomib with other anti-myeloma drugs could further improve the results achieved with bortezomib alone. We have recently initiated a prospective study to assess the combination of velcade, melphalan and prednisone (MPV) in patients with previously untreated MM. The primary objectives of this study are toxicity, feasibility and CR rate after 4 cycles. The regimen consisted of bortezomib 1.3 mg/m2 iv on day 1,4,8,11. melphalan 6 mg/m2 po, and prednisone 60 mg/m2 po given on days 1 through 7 of each cycle. As July 2005, 11 patients have been recruited. The median age is 64 (48–74) and all patients were Durie-Salmon stage IIIA. Nine of the 11 patients have completed ≥2 cycles of therapy, 6 patients have completed all 4 cycles of therapy and 3 patients were withdrawn from study (2 for pneumonia and 1 for grade 3 orthostatic hypotension). The most common adverse events were neuropathy (grade 1–3), neutropenia (grade 1–3), thrombocytopenia (grade1–3), fatigue, and bowel changes. For the 6 patients that have completed all 4 cycles of MPV, the responses were: 2/6 CR (negative SPEP/IFE); 1/6 very good partial remission (VGPR, 90% reduction of M-spike) and 3/6 partial remission (PR, 50% reduction of the serum M-spike). For the 3 patients who have completed only 2 cycles of therapy so far, 1/3 achieved a VGPR and 2/3 achieved a PR. Three patients have proceeded to stem cell collection and all engrafted following high dose therapy. Although experience is still limited and follow-up short, other than 3 patients withdrawn from study, all patients treated with MPV have responded to treatment and 2/6 patients achieved a CR. The best response was observed after cycle 2 in the majority of patients. Stem cell collection and engraftment was successful in all attempts so far. These data indicate that bortezomib combined with a short term alkylating regimen should be further explored as an induction regimen before transplantation in patients with myeloma.

Sequential VAD (Vincristine, Adriamycin, Dexamethasone) and VTD (VELCADE®, Thalidomide, Dexamethasone) Induction Followed by High-Dose Therapy with Autologous Stem Cell Transplantation and Maintenance Treatment with VELCADE for Newly Diagnosed Multiple Myeloma: Interim Results of Phase II Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 952-952 ◽  
Author(s):  
Sung-Soo Yoon ◽  
Hye Jin Kim ◽  
Dong Soon Lee ◽  
Hyeon Seok Eom ◽  
Jun Ho Jang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Maintenance Treatment ◽  
Response Rate ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Newly Diagnosed

Abstract Introduction Effective reduction of myeloma before autologous stem cell transplantation (ASCT) prolongs survival in multiple myeloma patients. Recently, incorporation of novel agents resulted in improved response rate and reduced side effect in newly diagnosed multiple myeloma. Method: Patients are planned to receive 2 cycles of VAD (vincristine 0.4mg D1-4, adriamycin 9mg/m2 D1-4, dexamethasone 40mg D1-4, 9–12 every 3 weeks), and VTD (bortezomib 1.3mg/m2 D1, 4, 8, 11, thalidomide 100mg daily, dexamethasone 40mg D1-4, 9–12 every 3 weeks). High dose melphalan (200mg/m2) is used as a conditioning regimen for ASCT. Bortezomib (1.3mg/m2) as a maintenance treatment is administered weekly x 4 times every 6 weeks for 4 cycles after ASCT. Response was assessed by EBMT criteria, with additional category of nCR. Adverse events were graded by the NCI-CTCAE, Version 3.0. Result: At this interim analysis, 60 patients have been entered into the ongoing trial, and efficacy could be assessed in 53 patients. After 2 cycles of VAD, response rate was 70%. After VTD, two patients showed further improvement with additional CR, and an overall response was 97% with 14% CR. Especially, patients with poor prognostic cytogenetics (n=6) all responded after VTD. So far, autologous stem cells were successfully collected in all 28 patients with a median CD34+ count of 7.8 x 106/kg (range, 2.17–44.7 x 106/kg). In 24 patients who underwent autologous stem cell transplantation, five patients gained additional CR. There was no progression in patients completed bortezomib maintenance (n=9, CR 77%). The median follow-up duration was 6 months, median time to response was 1.4 months, and median overall survival was not reached. Grade 3,4 hematologic toxicity was more frequently observed after VAD than VTD (anemia 15.8%, 4.6%, neutropenia 7.9%, 3.5%), and incidence of grade 2,3 peripheral neuropathy was low (VAD 3.5%, VTD 7%). Conclusion: Sequential VAD and VTD induction therapy in newly diagnosed multiple myeloma was highly effective, even in patients with poor prognostic cytogenetics, and did not prejudice stem cell collection. VTD could have contributed to increased RR and minimized side effects. An updated results will be presented at the ASH meeting. *Protocol Number: KMM51-NCT00378755.

Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients with Renal Insufficiency: a Single Centre Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4362-4362
Author(s):  
Malgorzata Krawczyk-Kulis ◽  
Slawomira Kyrcz-Krzemien ◽  
Tomasz Czerw ◽  
Monika Zielinska ◽  
Grazyna Bober
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Stem Cell ◽  
Renal Insufficiency ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Regeneration Time ◽  
Ckd Stage ◽  
Stem Cell Collection

Abstract Abstract 4362 BACKGROUND AND AIMS Multiple myeloma (MM) might be a cause a of the malignancy-related renal insufficiency, often present at diagnosis. Severity of it implicates further therapy. Patients with severe renal failure are generally excluded from high dose therapy even though they display a poor prognosis with conventional chemotherapy regimens. The goal of this study was to evaluate the eligibility and efficacy of autologous hematopoietic stem cell transplantation (AHCT) in MM patients with concomitant renal insufficiency. 239 MM patients were treated in our department with high-dose chemotherapy followed by AHCT between 1993 and 2009. Twenty of them (8%) were also diagnosed with renal impairment. PATIENTS AND METHODS 20 patients (8 women, 12 men), age 40-65 years (median 51) were enrolled. MM subtype at diagnosis was: IgG, n=14 (kappa-9, lambda-5); IgA kappa, n=1; light chain disease (LCD), n=4 (kappa-3, lambda-1); non-secretory, n=1. Chronic kidney disease (CKD) stage at MM diagnosis was 2-5 (median 3). One pt. was on chronic hemodialysis, two required plasmapheresis. Before AHCT pts. were treated with 1-4 (1) regimens, mainly VAD and CTD. 8/20 pts. received radiotherapy. Mobilization regimen was high-dose cyclophosphamide in 8 and IVE (iphosphamide, etoposide, epirubicin) in 12 cases. Stem cell collection yield was effective in all pts. (median 17.6 (1.9 - 44.7) x 10e6 CD34+ cells/kg). Disease stage at AHSCT: CR n=6, VGPR n=2, PR n=12. RESULTS Renal function measured before transplantation significantly improved due to MM treatment compared to that at diagnosis, p=0.008. CKD stage before transplantation equaled 1-4 (median 2). The only one patient who initially required hemodialysis became dialysis independent before AHCT. Conditioning regimen with melphalan (range 75-200mg/m2) was generally well tolerated. The median numbers of transplanted cells were following: NC 2.5 (1-7.6) x10e8/kg; CD34+ 7.9 (0.8-21.7) x 10e6/kg. All patients engrafted. Median regeneration time of granulocytes up to >0.5 G/l and of platelets to >50 G/l equaled 14 (12-19) and 14 (12-101) days, respectively. Transplant related mortality at day 100 was 0%. Mucositis, diarrhoea, bacterial and HSV infections were main complications after AHCT. Regeneration time, hospital stay, days of intravenous antibiotics or antifungal drugs administration and number of transfusion were comparable to pts. transplanted without renal impairment. No renal complications were observed. On the contrary creatinine clearance after transplantation showed trend towards further improvement compared to that before AHCT, p=0.07. The probability of overall (OS) and progression free (PFS) survival for studied group of pts. were 84% and 63%, respectively. Median observation time 2.3 years (0.1-12.5). CONCLUSIONS Our observation demonstrates that AHCT is an effective and well tolerated option for MM patients with mild or moderate renal insufficiency. Treatment before transplantation and also high-dose chemotherapy followed by AHCT may even improve renal function. No relationship between CKD and stem cell collection yield, engraftment or severity of post-transplant complications was observed in this group of patients. Disclosures: No relevant conflicts of interest to declare.

A Comparison of Chemotherapy + G-CSF Versus Plerixafor (Mozobil®) + G-CSF for Stem Cell Mobilization In Patients with Multiple Myeloma Treated with Lenalidomide

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2258-2258
Author(s):  
Tomer M Mark ◽  
Adriana C Rossi ◽  
Roger N Pearse ◽  
Morton Coleman ◽  
David Bernstein ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Yield ◽  
High Dose ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Stem Cell Collection

Abstract Abstract 2258 Background: Prior use of lenalidomide beyond 6 cycles of therapy in the treatment of multiple myeloma (MM) has been shown to negatively impact stem cell yield, but this phenomenon can be overcome with the addition of high-dose cyclophosphamide to standard G-CSF mobilization. We hypothesized that the use of plerixafor (Mozobil®) would compare similarly to chemotherapy in rescuing the ability to collect stem cells in lenalidomide-treated myeloma. Methods: We performed a retrospective study comparing the efficacy of plerixafor + G-CSF mobilization (PG) to chemotherapy + G-CSF (CG) (either high-dose cyclophosphamide at 3g/m2 or DCEP [4-day infusional dexamethasone/ cyclophosphamide/ etoposide/cisplatin]) in 49 consecutive stem cell collection attempts in patients with MM exposed to prior lenalidomide. The primary endpoint was the ability to collect sufficient stem cells for at least two transplants (minimum 5×106 CD34+ cells/kg), comparing results in terms of total exposure to lenalidomide and time elapsed from lenalidomide exposure until the mobilization attempt. The secondary endpoint was number of apheresis days required to meet collection goal. Resilts: Twenty-four patients underwent PG mobilization and twenty-five with CG (21 with G-CSF + cyclophosphamide, 4 with G-CSF+DCEP). The two groups did not differ in terms of total amount of lenalidomide exposure: median number of lenalidomide cycles for patients mobilized with PG was 6.5 (range 1.2–86.6), vs. 6 (range 2–21.6), for patients mobilized with CG (P = 0.663). The median time between mobilization and last lenalidomide dose was also similar between the two groups: 57.5 (range 12–462) days for PG vs. 154 (range 27–805) days for CG (P = 0.101). There was an equivalent rate of successful collection of 100% for PG and 96% for CG, P = 0.322. One patient failed collection in the CG group due to emergent hospitalization for septic shock during a period of neutropenia; no patient collected with PG had a serious adverse event that interrupted the collection process. Stem cell yield did not differ between the two arms (13.9 vs. 18.8 × 106 million CD34+ cells/kg for PG vs. CG respectively, P = 0.083). Average time to collection goal was also equal, with a median of time of 1 day required in both groups, (range 1–2 days for PG, 1–5 days for CG, P = 0.073). There was no relationship between amount of lenalidomide exposure and stem cell yield with either PG (P = 0.243) or CG (P = 0.867). Conclusion: A plerixafor + G-CSF mobilization schedule is equivalent in efficacy to chemotherapy + G-CSF in obtaining adequate numbers of stem cells for two autologous stem cell transplants in patients with MM exposed to lenalidomide; however, PG may be a less toxic approach than chemomobilization. Number of lenalidomide cycles has no impact on chances of stem cell collection success using either method. Disclosures: Mark: Celgene Corp: Speakers Bureau; Millenium Corp: Speakers Bureau. Zafar: Celgene Corp: Speakers Bureau. Niesvizky: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Consultancy, Research Funding.

scholarly journals Vinorelbine-Cyclophosphamide Compared to Cyclophosphamide in Peripheral Blood Stem Cell Mobilization for Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3103-3103
Author(s):  
Sanjay De Mel ◽  
Yunxin Chen ◽  
Adeline Lin ◽  
Eng Soo Yap ◽  
Teck Guan Soh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
P Value ◽  
High Dose ◽  
Haematopoietic Progenitor Cell ◽  
Cd 34 ◽  
Transfusion Requirements ◽  
Grade 3 ◽  
Stem Cell Collection

Abstract Background High dose therapy (HDT) followed by autologous stem cell rescue is the standard of care for transplant eligible patients with multiple myeloma (MM). High dose cyclophosphamide (Cy) at 4-7g/m2 with granulocyte colony stimulating factor (GCSF) has been shown to be effective for haematopoietic progenitor cell (HPC) mobilization despite associated haematologic toxicity.Vinorelbine 25mg/m2 in combination with Cy 1500mg/m2 (Vino-Cy) was shown to be comparable to Cy mobilization in a study using historical controls. Vino-Cy is the mobilization regimen of choice at the National University Hospital Singapore (NUH) while Cy mobilization is preferred at the Singapore General Hospital (SGH). We present a retrospective comparison of HPC mobilisation outcomes using Vino- Cy and Cy at these institutions. Methods Medical records for patients undergoing HPC mobilization between 2004 and 2014 at NUH and SGH were analysed. Patients mobilized with Vino -cy received Vinorelbine 25mg/m2 on day 1 followed by cyclophosphamide 1500mg/m2 on day 2, GCSF 10mcg/kg/day was given from day 4 onwards. Alternatively, pegylated GCSF 6mg was given on day 4. Patients mobilized with Cy were given cyclophosphamide 1500mg/m2 on day 1 and 2 and GCSF 10mcg/kg/day from day 5 onwards. Apheresis (using the cobe spectra or optia system at NUH and the Haemonetics MCS+ system at SGH) was commenced once a peripheral blood CD 34+ count of >/= 10 x 10 6/l was achieved. The number of total blood volume exchanges per apheresis was 3 at NUH and 4 at SGH. Apheresis was continued until a minimum target CD 34 collection of 5 x 10 6 per kg/BW was reached. Patients who were successfully mobilized proceeded to HDT with melphalan 200mg/m2. Results 133patients underwent HPC mobilization between 2004 and 2014. The median weight was 62 Kg for Vino Cy and 58Kg for the Cy patients (p=0.03). The groups were evenly matched in terms of age, presence of renal impairment, bone lesions, ISS stage and the use of novel agent based induction. Bortezomib based induction was used in 73% of Vino-Cy and 43% of Cy patients. A higher percentage of Cy patients were mobilized in complete remission (53%) compared to Vino-Cy (21%). Table 1 summarises the mobilization outcomes of the two groups. Although the total CD 34+ collection was greater in the Cy group, the difference in the percentage of patients achieving an adequate HPC collection was not statistically significant, 72/84 (85%) of Vino-Cy patients and 45/47 (95%) of Cy patients achieved a stem cell collection of greater than 5 x 10 6/Kg BW (P=0.07). There were two mobilization failures in each group, one of whom (a Vino-Cy patient) was previously treated with melphalan. The number of days taken to achieve an adequate peripheral blood HPC count was shorter in the Vino Cy group and the date of harvest was also more predictable for Vino Cy with a standard deviation of 0.95 compared to 1.95 for Cy. Grade 3-4 harvest related complications were significantly more common in the Cy group (table 2). There was no significant drop in haemoglobin after harvest in either group. Discussion Our data suggest that HPC mobilization maybe more effective with Cy, differing from data published by Annunziata et al which showed a superior HPC mobilization with Vino-Cy compared to the historical Cy control. Vino-Cy appears superior in terms of the time taken for an adequate peripheral CD34+ count and predictability of the day of harvest. The incidence of harvest related complications is also greater for Cy. These findings are common to our cohort and that reported by Annunziata et al. Data on transfusion requirements, hospitalization rates and survival are being collected. Prospective clinical trials are required to definitively determine which protocol is superior. Table 1. Day of protocol when harvest took place P value Number of days taken to harvest P value CD34+/Kg Collected P value Vino-Cy(n=84) Cy(n=47) Vino-Cy(n=84) Cy(n=47) Vino-Cy(n=84) Cy(n=47) Median 9 13 P=0.000 2 2 P=0.97 8.4 11.3 P=0.009 Mean 8.5 12 2 2 10.0 16.2 Maximum 11 16 5 5 32.5 73.9 Minimum 5 7 1 1 2.2 2.4 SD 0.95 1.9 0.94 0.93 5.7 14.5 Table1. Comparison of Mobilisation Outcomes with Vino-Cy and Cy. Table 2. Mobilisation Chemotherapy P value. Vino-Cy(84) Cyclophosphamide (47) Complications during and after harvest (grade3-4) 2(2.3) 9(19) 0.009 Fluid Overload 1 0 Neutropaenic Fever 1 8 Line related thrombosis 0 1 Table 2. Grade 3-4 Complications during and after stem cell collection, data presented as number (%). Disclosures No relevant conflicts of interest to declare.

The Optimal Timing for Stem Cell Collection After Induction Therapy for Patients with Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2252-2252
Author(s):  
Aziz Nazha ◽  
Dan T. Vogl ◽  
Una O'Doherty ◽  
Patricia Mangan ◽  
Kathleen Cunningham ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Conflicts Of Interest ◽  
Optimal Timing ◽  
High Dose ◽  
Cell Transplant ◽  
Cd 34 ◽  
The Mean ◽  
Stem Cell Collection

Abstract Abstract 2252 Introduction: High dose chemotherapy and stem cell transplant remains an integral part of the therapy for Multiple Myeloma patients under age of 70. The collection of sufficient number of stem cells for one or more transplant is however sometimes a challenge. Moreover, the optimal timing for stem cell collection after induction chemotherapies is controversial. The standard recommendation is for stem cell collection after 4–6 cycles of non-alkylator regimen, however studies to support this practice are limited. Material and Method: We conducted a retrospective analysis of 366 patients who were diagnosed with multiple myeloma and mobilized at the Hospital of University of Pennsylvania between January 2002 and December 2008. Patients who did not meet the initial inclusion criteria were those who had induction regimens containing an alkalytor agent or whose regimens were not well documented and were excluded from futher analysis (85). Every 4 cycles of any non-alkalytor agent was considered to be one treatment session for the purpose of this analysis. 245 patients received 1 or 2 treatment sessions and 36 received > 2. All patients were mobilized with either Cyclophosphamide/G-CSF (CY/G-CSF), Plerixafor/G-CSF (AMD/G-CSF), or G-CSF alone. Result: The mean number of collected CD 34+ cells (CD 34+) was 9.22 × 106 CD34+/Kg in the patients who received 1 or 2 sessions and 6.87 × 1106 CD34+/Kg in the patients who received > 2 sessions (P= 0.005). The number of the patients who collected > 6 × 106 CD34+/Kg was 63%(153/246), 53%(19/36) respectively, (p= 0.005). The patients who mobilized with either CY/G-CSF or AMD/G-CSF collected higher number of CD34+ than the patients mobilized with G-CSF alone in both groups. (Table 1, 2.) The mean number of collected stem cells was 7.14 × 106 CD34+/Kg in the patients who received more than 2 sessions of different regimens and 6.26 × 106 CD34+/Kg in the patients who received > 2 sessions of the same regimen. Conclusion: The patients who mobilized after fewer than 8 cycles of non-alkylator agents (2 sessions) collected a higher number of CD 34+ than those with greater than 8 cycles. CY/G-CSF or AMD/G-CSF are similar and superior to G-CSF alone in the more heavily treated patients. The patients who received multiple sessions of the same regimen have similar outcome compared to those who received multiple different regimens suggesting that the duration of the treatment may impact stem cell collection more than the content of the regimen. Prospective studies in this regards are warranted. Disclosures: No relevant conflicts of interest to declare.

Stem Cell Mobilization after Various Induction Regimens in Patients with Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5433-5433
Author(s):  
Jakub Radocha ◽  
Vladimir Maisnar ◽  
Miriam Lanska ◽  
Jiri Hanousek ◽  
Katerina Machalkova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Conflicts Of Interest ◽  
Rapid Development ◽  
Autologous Transplantation ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Cell Transplant ◽  
Cell Mobilization ◽  
Stem Cell Collection

Abstract Stem cell mobilization after various induction regimens in patients with multiple myeloma Introduction: Rapid development of novel therapies for multiple myeloma has led to a significant improvement in response to the treatment. Stem cell mobilization before autologous stem cell transplantation is a source of considerable costs of transplant procedure. Whether modern induction regimens affect outcome of stem cell mobilization has not been extensively studied. Aim: The goal of this study was to compare efficacy of stem cell mobilization after different induction regimens in patients with multiple myeloma. The primary goal was to compare CTD (cyclophosphamide, thalidomide, dexamethasone), CVD (cyclophosphamide, bortezomib, dexamethasone) and VTD (bortezomib, thalidomide, dexamethasone) and regimens in terms of succesful stem cell collection. Methods: All patients with multiple myeloma who have been planned for stem cell collection and were treated with one of the above mentioned regimens were included in this retrospective analysis. The demographic data, amount of stem cells collected, number of days needed to reach the target collection were recorded. All patients received high dose cyclophosphamide 2,5 g/m2 prior to stem cell collection and were primed with G-CSF twice daily from day 5. The collection was started at day 10. Collection goal was 8x106/kg CD34+ cells. Results: 15 patients received CTD, 25 patients CVD and 16 patients VTD regimen before stem cell collection. Groups were comparable according to age, gender and myeloma stages. Mean collected cells at the end of collection were 9.2 (SD 2.8) for CTD, 12.3 (SD 5.6) for CVD and 10.1 (SD 2.1) for VTD (p=0.066). Mean daily harvest was 3.4, 8.0 and 7.6 x106/kg respectively (p=0.01). Mean days needed to reach desired harvest were 3, 2.25 and 1.6 days (p=0.001). No collection failure was observed. Conclusion: The best collection results were seen in patients after induction with CVD or VTD regimen. VTD regimen also required the least days for collection and seems to be most beneficial for cost of collection. CTD regimen shows the least efficacy in stem cell collection before autologous transplantation. All patients managed to harvest for at least one stem cell transplant. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals One-Day Low-Dose Etoposide Is an Effective Chemomobilization Regimen with Minimal Toxicity for Autologous Stem Cell Transplantation in Patients with Multiple Myeloma: A Multicenter Study from Tertiary Hospitals in Korea

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3347-3347
Author(s):  
Yong Park ◽  
Dae Sik Kim ◽  
Ka-Won Kang ◽  
Byung-Hyun Lee ◽  
Eun Sang Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Febrile Neutropenia ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Low Dose ◽  
High Dose ◽  
Tertiary Hospitals ◽  
Stem Cell Collection

Abstract Purpose Autologous stem cell transplantation (ASCT) is widely used as a part of induction treatment for transplantation-eligible patients with multiple myeloma. For successful ASCT, mobilizing hematopoietic stem cells from bone marrow to peripheral blood is essential because collecting a sufficient number of stem cells using apheresis is mandatory. As a method for mobilization, chemomobilization consisting of high-dose chemotherapy plus granulocyte-colony stimulating factor (G-CSF) or G-CSF alone (G-mobilization) has been used. However, the mobilization failure still remains a problematic issue. Given repeated mobilization attempts increase medical costs and the risk of morbidity related with apheresis, the mobilization process should be efficient. Chemomobilization is more effective than G-mobilization, however, chemomobilization has the risk of complication such as febrile neutropenia or chemotherapy-induced second malignancy. Thus, we compared the efficacy and safety of our new chemomobilization regimen, one-day low-dose etoposide with that of two-day low-dose etoposide, one-day high-dose cyclophosphamide, and G-mobilization. Methods We retrospectively analyzed 234 patients who underwent ASCT for MM between 2008 and 2018 in four tertiary hospitals in Korea. One-day low-dose etoposide regimen (E1) was the intravenous (IV) administration of etoposide (375 mg/m2) over 4 hours whereas two-day low-dose etoposide (E2) was the same dose of etoposide on 1st and 2nd day in outpatient clinic. G-CSF administration was started around on 10th day until the end of collection. In G-mobilization regimen (G), the injection of G-CSF was started four days (day -4) before initiation of apheresis (day 0), and G-CSF once a day was maintained untill the end of collection. One-day high-dose cyclophosphamide regimen (C) was the IV administration of cyclophosphamide (3.5 g/m2) on 1st day and the daily injection of G-CSF from 2nd day until the end of stem cell collection. Peripheral blood stem cell collection was started when CD34-positive cells or hematopoietic progenitor cells were more than 5000/μL in peripheral blood, or white blood cell count was more than 5000/μL. In this study, we defined the 'adequate mobilization' as CD34-positive cells more than 4ⅹ106/kg, and 'mobilization failure' as a collected CD34-positive cells less than 2ⅹ106/kg. Neutrophil and platelet engraftment was defined as more than 500/μL and 20,000/μL on consecutive two days, respectively. Results 31 patients received single dose etoposide (E1) between 2016 and 2018 whereas 28 patients received double dose etoposide (E2) between 2011 and 2018. The other two regimens were used in 105 (C, 2008-2015) and 70 patients (G, 2008-2017) according to physicians' decision. The comparison of four regimens showed the median CD34-positive cells of E1 regimen was 5.57ⅹ106/kg that was comparable to that of E2 and C (Table 1). The number of CD34-positive cells on 1st day of apheresis was 4.03ⅹ106/kg in E1 regimen, and it was higher than that of C and G (3.32 and 1.79ⅹ106/kg, respectively). As a result, E1 regimen achieved 'adequate mobilization' in 100% of patients (n=30) like E2 regimen (n=28, 100%). Mobilization failure did not occur in E1 and E2 regimens whereas 4-10% of patients experienced mobilization failure in C and G regimens (Table 1). All patients receiving E1 and E2 regimen but one patient in E1 could collect more than 4ⅹ106/kg of CD34-positive cells within three cycles of apheresis. The occurrence of febrile neutropenia was extremely lower in E1 regimen (7%) than E2 and C regimens (43% and 34%, respectively, p<0.001). Both neutrophil and platelet engraftment were the fastest in E1 (the median 9 days after ASCT, p<0.001). Conclusions One-day low-dose etoposide administration could be effective for chemomobilization in myeloma patients with reduced risk of complication compared to two-day low-dose etoposide, high-dose cyclophosphamide and G-mobilization. Table 1. Table 1. Disclosures No relevant conflicts of interest to declare.

Modified Thalidomide, Cyclophosphamide and Dexamethasone (TCD) to Patients with Multiple Myeloma as Primary Therapy Prior to Peripheral Blood Stem Cell Collection.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5173-5173
Author(s):  
Deok-Hwan Yang ◽  
Je-Jung Lee ◽  
Yeo-Kyeoung Kim ◽  
Jin-Ho Baek ◽  
Sang-Kyun Sohn ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Complete Response ◽  
Blood Stem Cell ◽  
High Dose ◽  
Primary Therapy ◽  
Hematopoietic Stem ◽  
Stem Cell Collection

Abstract In the treatment of multiple myeloma (MM), autologous peripheral blood stem cell (PBSC)-supported high-dose melphalan is now considered standard therapy, especially for younger patients. Before PBSC, a new immunomodulatory drug, thalidomide, has replaced VAD regimen as the induction therapy of choice prior to hematopoietic stem cell procurement. Thalidomide has alternative mechanisms of action and usually combines with dexamethasone or alkylating agent, but the optimal doses and the intervals of chemotherapy has been evaluated. We reported preliminary data that the patients with previously untreated multiple myeloma were treated by combined different dose-scheduled thalidomide, cyclophosphamide, and dexamethasone as primary therapy and performed autologous stem cell collection. A total of 52 patients with MM were initially treated thalidomide-based chemotherapy from June 2003. Thalidomide was given with the three different method: 400mg/day on D1–5, D15–19 (arm A), 50mg/day daily (arm B) combined with cyclophosphamide 150mg/m2 P.O. on D1–4 and dexamethasone 20mg/m2 P.O. or I.V. on D1–5, D15–19, or thalidomide 200mg/day daily combined with dexamethasone 20mg/m2 on D1–4, 9–12, 17–20 in odd cycles and on D1–4 in even cycles (arm C), repeated every 28 days. Low-dose aspirin or warfarin was taken as prophylaxis for thrombosis. Thirty-nine (arm A: 17, arm B: 12, arm C: 10) of the 52 patients who received at least 4 cycles or more were evaluated for response and toxicity. Median age was 65 (range: 39–80) years and the total number of 158 cycles of toxicities were evaluated. After median 4 months of time to response followed, the overall response rate was 71.8% (76.5% v 75.0% v 60.0%), including 23% (17.5% v 23% v 28%) of complete or near complete response. Two patients (5.1%) died due to infection during treatment. When the toxicity of therapy was evaluated with more Grade III, two patients (5.1%) showed neurotoxicity, six patients (15.4%) showed neutropenia, and two patients (5.1%) had deep-vein thrombosis. Thirteen patients who achieved more than partial response proceeded to PBSC collection and yielded a median number of 3.78 x 106 CD 34+ cells/kg. This low or intermediate dose or periodic thalidomide combination showed positive responses, reducing toxicities, and adequate numbers of blood stem cells in patients eligible for subsequent high-dose chemotherapy.

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